Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Novel Aspects in Kidney Disease in Diabetes

Special Issue Editors
Special Issue Information
Keywords
Related Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 49071

Share This Special Issue

Special Issue Editors

Prof. Dr. Giuseppina T. Russo

E-Mail Website
Guest Editor

Department of Clinical and Experimental Medicine, Policlinico Universitario “G. Martino”, Via Consolare Valeria, 98124 Messina, Italy
Interests: diabetes; diabetic kidney disease; gender medicine; macrovascular disease; lipid metabolism; homocysteine; genetics
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Domenico Santoro

E-Mail Website
Guest Editor

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Interests: renal disease; glomerulonephritis; hemodialysis; renin angiotensin system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes mellitus (DM) affects millions of people worldwide, and ~40% of them may have diabetic nephropathy.

We are witnessing a dramatic change in the pathophysiology, management and therapeutic approach of diabetic nephropathy, now termed kidney disease associated with DM. Accumulating evidence has recently been focused on clarifying the different morphological and pathophysiological aspects of renal lesions associated with diabetes, especially the non-albuminuric phenotype. There is still an ongoing debate on the prevalence and the role of different forms of kidney disease in diabetic subjects, other than diabetic kidney disease and the potential biomarkers able to distinguish among them, when the biopsy is not feasible. Renewed hope comes from the recent evidences from experimental research, and from cardiovascular outcomes trials (CVOTs), which have demonstrated the benefits of the new classes of hypoglycemic drugs on the occurrence and progression of kidney disease as well as on cardiovascular disease (CVD) risk. Finally, the high CVD risk in DM subjects with kidney disease calls for the urgent need to translate basic research into clinical practice, in order to help people with DM to survive longer and without the specter of dialysis in front of them.

This Special Issue will deal with several aspects of diabetes and its renal complications, as specified below. We welcome original research articles, comprehensive reviews and short communications with a focus on molecular level studies.

Potential topics include, but are not limited to, the relationship between kidney disease associated with diabetes with:

1. Sex/gender differences;

2. Renal morphology changes in diabetic patients;

3. Differences between Type 1 and type 2 diabetes;

4. Role of genetics/omics

5. Predictive models/artificial intelligence;

6. New biomarkers/new applications of old biomarkers;

7. Phenotyping DKD: isolated low eGFR vs. albuminuria;

8. New approaches with albuminuria: overcoming traditional cut-offs;

9. Role of the renin–angiotensin system and SGT2i;

10. Predictors of fast progression in patients with diabetes mellitus and renal failure;

11. Role of vitamin D status in diabetic patients with renal disease;

12. Management of Diabetic Mellitus in patients with reduced renal function;

13. Oxidative stress/endothelial dysfunction/inflammation and the progression of diabetic nephropathy;

14. Potential beneficial effects of SGTL2 inhibitors and GLP1-RAs and/or their combination;

15. Mineral corticoid receptor antagonist and diabetes mellitus;

16. Ageing, kidney and diabetes management;

17. Cardiovascular risk factors and diabetic kidney;

18. Nutritional aspects in diabetic patients with chronic renal failure.

Prof. Dr. Giuseppina T. Russo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

diabetic kidney disease
microalbuminuria
gender
genetics, omics, artificial intelligence, biomarkers
low protein diet in diabetic nephropathy
ageing
sglt2
glp1-ras

Related Special Issue

Novel Aspects in Kidney Disease in Diabetes 2.0 in International Journal of Molecular Sciences (3 articles)

Published Papers (13 papers)

Download All Papers

Research

Jump to: Review

15 pages, 3521 KiB

Open AccessArticle

Redefining the Role of ADAM17 in Renal Proximal Tubular Cells and Its Implications in an Obese Mouse Model of Pre-Diabetes

by Vanesa Palau, Sofia Villanueva, Josué Jarrín, David Benito, Eva Márquez, Eva Rodríguez, María José Soler, Anna Oliveras, Javier Gimeno, Laia Sans, Marta Crespo, Julio Pascual, Clara Barrios and Marta Riera

Int. J. Mol. Sci. 2021, 22(23), 13093; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313093 - 03 Dec 2021

Cited by 4 | Viewed by 2165

Abstract

Acute and chronic kidney lesions induce an increase in A Disintegrin And Metalloproteinase domain 17 (ADAM17) that cleaves several transmembrane proteins related to inflammatory and fibrotic pathways. Our group has demonstrated that renal ADAM17 is upregulated in diabetic mice and its inhibition decreases renal inflammation and fibrosis. The purpose of the present study was to analyze how Adam17 deletion in proximal tubules affects different renal structures in an obese mice model. Tubular Adam17 knockout male mice and their controls were fed a high-fat diet (HFD) for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, and pro-inflammatory and pro-fibrotic markers were evaluated. Results showed that wild-type mice fed an HFD became obese with glucose intolerance and renal histological alterations mimicking a pre-diabetic condition; consequently, greater glomerular size and mesangial expansion were observed. Adam17 tubular deletion improved glucose tolerance and protected animals against glomerular injury and prevented podocyte loss in HFD mice. In addition, HFD mice showed more glomerular macrophages and collagen accumulation, which was prevented by Adam17 deletion. Galectin-3 expression increased in the proximal tubules and glomeruli of HFD mice and ameliorated with Adam17 deletion. In conclusion, Adam17 in proximal tubules influences glucose tolerance and participates in the kidney injury in an obese pre-diabetic murine model. The role of ADAM17 in the tubule impacts on glomerular inflammation and fibrosis. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

13 pages, 107854 KiB

Open AccessArticle

L-NAME Administration Enhances Diabetic Kidney Disease Development in an STZ/NAD Rat Model

by Raphaëlle Corremans, Patrick C. D’Haese, Benjamin A. Vervaet and Anja Verhulst

Int. J. Mol. Sci. 2021, 22(23), 12767; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312767 - 25 Nov 2021

Cited by 8 | Viewed by 2573

Abstract

One of the most important risk factors for developing chronic kidney disease (CKD) is diabetes. To assess the safety and efficacy of potential drug candidates, reliable animal models that mimic human diseases are crucial. However, a suitable model of diabetic kidney disease (DKD) is currently not available. The aim of this study is to develop a rat model of DKD by combining streptozotocin and nicotinamide (STZ/NAD) with oral N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) administration. Diabetes was induced in male Wistar rats by intravenous injection of 65 mg/kg STZ, 15 min after intraperitoneal injection of 230 mg/kg NAD. Rats were assigned to different groups receiving L-NAME (100 mg/kg/day) (STZ/NAD/L-NAME) or vehicle (STZ/NAD) for a period of 9 or 12 weeks by daily oral gavage. All rats developed hyperglycemia. Hyperfiltration was observed at the start of the study, whereas increased serum creatinine, albumin-to-creatinine ratio, and evolving hypofiltration were detected at the end of the study. Daily L-NAME administration caused a rapid rise in blood pressure. Histopathological evaluation revealed heterogeneous renal injury patterns, which were most severe in the STZ/NAD/L-NAME rats. L-NAME-induced NO-deficiency in STZ/NAD-induced diabetic rats leads to multiple characteristic features of human DKD and may represent a novel rat model of DKD. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

12 pages, 1896 KiB

Open AccessArticle

A Computational Model of Kidney Function in a Patient with Diabetes

by Rui Hu and Anita Layton

Int. J. Mol. Sci. 2021, 22(11), 5819; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115819 - 29 May 2021

Cited by 14 | Viewed by 3298

Abstract

At the onset of diabetes, the kidney grows large and the glomerular filtration rate becomes abnormally high. These structural and hemodynamics changes affect kidney function and may contribute to the development of chronic kidney disease. The goal of this study is to analyze how kidney function is altered in patients with diabetes and the renal effects of an anti-hyperglyceamic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish that goal, we have developed a computational model of kidney function in a patient with diabetes and conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Simulation results indicate that diabetes-induced hyperfiltration and tubular hypertrophy enhances Na⁺ transport, especially along the proximal tubules and thick ascending limbs. These simulations suggest that SGLT2 inhibition may attenuate glomerular hyperfiltration by limiting Na⁺-glucose transport, raising luminal [Cl⁻] at the macula densa, restoring the tubuloglomerular feedback signal, thereby reducing single-nephron glomerular filtration rate. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

16 pages, 2518 KiB

Open AccessArticle

Effects of Environmental Conditions on Nephron Number: Modeling Maternal Disease and Epigenetic Regulation in Renal Development

by Lars Fuhrmann, Saskia Lindner, Alexander-Thomas Hauser, Clemens Höse, Oliver Kretz, Clemens D. Cohen, Maja T. Lindenmeyer, Wolfgang Sippl, Manfred Jung, Tobias B. Huber and Nicola Wanner

Int. J. Mol. Sci. 2021, 22(8), 4157; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084157 - 16 Apr 2021

Cited by 4 | Viewed by 2893

Abstract

A growing body of evidence suggests that low nephron numbers at birth can increase the risk of chronic kidney disease or hypertension later in life. Environmental stressors, such as maternal malnutrition, medication and smoking, can influence renal size at birth. Using metanephric organ cultures to model single-variable environmental conditions, models of maternal disease were evaluated for patterns of developmental impairment. While hyperthermia had limited effects on renal development, fetal iron deficiency was associated with severe impairment of renal growth and nephrogenesis with an all-proximal phenotype. Culturing kidney explants under high glucose conditions led to cellular and transcriptomic changes resembling human diabetic nephropathy. Short-term high glucose culture conditions were sufficient for long-term alterations in DNA methylation-associated epigenetic memory. Finally, the role of epigenetic modifiers in renal development was tested using a small compound library. Among the selected epigenetic inhibitors, various compounds elicited an effect on renal growth, such as HDAC (entinostat, TH39), histone demethylase (deferasirox, deferoxamine) and histone methyltransferase (cyproheptadine) inhibitors. Thus, metanephric organ cultures provide a valuable system for studying metabolic conditions and a tool for screening for epigenetic modifiers in renal development. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

15 pages, 3110 KiB

Open AccessArticle

TP63 Is Significantly Upregulated in Diabetic Kidney

by Sitai Liang, Bijaya K. Nayak, Kristine S. Vogel and Samy L. Habib

Int. J. Mol. Sci. 2021, 22(8), 4070; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22084070 - 15 Apr 2021

Cited by 3 | Viewed by 2199

Abstract

The role of tumor protein 63 (TP63) in regulating insulin receptor substrate 1 (IRS-1) and other downstream signal proteins in diabetes has not been characterized. RNAs extracted from kidneys of diabetic mice (db/db) were sequenced to identify genes that are involved in kidney complications. RNA sequence analysis showed more than 4- to 6-fold increases in TP63 expression in the diabetic mice’s kidneys, compared to wild-type mice at age 10 and 12 months old. In addition, the kidneys from diabetic mice showed significant increases in TP63 mRNA and protein expression compared to WT mice. Mouse proximal tubular cells exposed to high glucose (HG) for 48 h showed significant decreases in IRS-1 expression and increases in TP63, compared to cells grown in normal glucose (NG). When TP63 was downregulated by siRNA, significant increases in IRS-1 and activation of AMP-activated protein kinase (AMPK (p-AMPK-Th¹⁷²)) occurred under NG and HG conditions. Moreover, activation of AMPK by pretreating the cells with AICAR resulted in significant downregulation of TP63 and increased IRS-1 expression. Ad-cDNA-mediated over-expression of tuberin resulted in significantly decreased TP63 levels and upregulation of IRS-1 expression. Furthermore, TP63 knockdown resulted in increased glucose uptake, whereas IRS-1 knockdown resulted in a decrease in the glucose uptake. Altogether, animal and cell culture data showed a potential role of TP63 as a new candidate gene involved in regulating IRS-1 that may be used as a new therapeutic target to prevent kidney complications in diabetes. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

15 pages, 2192 KiB

Open AccessArticle

The Effect of Far-Infrared Therapy on the Peritoneal Expression of Glucose Degradation Products in Diabetic Patients on Peritoneal Dialysis

by Chia-Ning Chang, Chih-Yuan Niu, Ann Charis Tan, Chia-Hao Chan, Chun-Fan Chen, Tz-Heng Chen, Szu-Yuan Li, Yung-Tai Chen, Fan-Yu Chen, Wen-Sheng Liu, Chih-Ching Lin and Guor-Jien Wei

Int. J. Mol. Sci. 2021, 22(7), 3732; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073732 - 02 Apr 2021

Cited by 8 | Viewed by 2779

Abstract

Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient’s gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

12 pages, 16379 KiB

Open AccessArticle

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

by Erasmia Sampani, Dimitra-Vasilia Daikidou, George Lioulios, Aliki Xochelli, Zoi Mitsoglou, Vasiliki Nikolaidou, Chrysostomos Dimitriadis, Asimina Fylaktou, Aikaterini Papagianni and Maria Stangou

Int. J. Mol. Sci. 2021, 22(6), 2975; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22062975 - 15 Mar 2021

Cited by 12 | Viewed by 1621

Abstract

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 1086 KiB

Open AccessReview

Incretins in the Therapy of Diabetic Kidney Disease

by Agnieszka Przezak, Weronika Bielka and Andrzej Pawlik

Int. J. Mol. Sci. 2021, 22(22), 12312; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212312 - 15 Nov 2021

Cited by 4 | Viewed by 1967

Abstract

Diabetic kidney disease is a microvascular complication that occurs in patients with diabetes. It is strongly associated with increased risk of kidney replacement therapy and all-cause mortality. Incretins are peptide hormones derived from the gastrointestinal tract, that besides causing enhancement of insulin secretion after oral glucose intake, participate in many other metabolic processes. Antidiabetic drug classes, such as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide receptor agonists, which way of action is based on incretins facility, not only show glucose-lowering properties but also have nephroprotective functions. The aim of this article is to present the latest information about incretin-based therapy and its influence on diabetic kidney disease appearance and progression, point its potential mechanisms of kidney protection and focus on future therapeutic possibilities bound with these two antidiabetic drug classes. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

18 pages, 736 KiB

Open AccessReview

TGF-Beta as a Master Regulator of Diabetic Nephropathy

by Li Wang, Hong-Lian Wang, Tong-Tong Liu and Hui-Yao Lan

Int. J. Mol. Sci. 2021, 22(15), 7881; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157881 - 23 Jul 2021

Cited by 73 | Viewed by 7163

Abstract

Diabetic nephropathy (DN) is one of the most common complications in diabetes mellitus and the leading cause of end-stage renal disease. TGF-β is a pleiotropic cytokine and has been recognized as a key mediator of DN. However, anti-TGF-β treatment for DN remains controversial due to the diverse role of TGF-β1 in DN. Thus, understanding the regulatory role and mechanisms of TGF-β in the pathogenesis of DN is the initial step towards the development of anti-TGF-β treatment for DN. In this review, we first discuss the diverse roles and signaling mechanisms of TGF-β in DN by focusing on the latent versus active TGF-β1, the TGF-β receptors, and the downstream individual Smad signaling molecules including Smad2, Smad3, Smad4, and Smad7. Then, we dissect the regulatory mechanisms of TGF-β/Smad signaling in the development of DN by emphasizing Smad-dependent non-coding RNAs including microRNAs and long-non-coding RNAs. Finally, the potential therapeutic strategies for DN by targeting TGF-β signaling with various therapeutic approaches are discussed. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

24 pages, 542 KiB

Open AccessReview

Gender Differences in Diabetic Kidney Disease: Focus on Hormonal, Genetic and Clinical Factors

by Annalisa Giandalia, Alfio Edoardo Giuffrida, Guido Gembillo, Domenico Cucinotta, Giovanni Squadrito, Domenico Santoro and Giuseppina T. Russo

Int. J. Mol. Sci. 2021, 22(11), 5808; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115808 - 28 May 2021

Cited by 42 | Viewed by 5914

Abstract

Diabetic kidney disease (DKD) is one of the most serious complications of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Current guidelines recommend a personalized approach in order to reduce the burden of DM and its complications. Recognizing sex and gender- differences in medicine is considered one of the first steps toward personalized medicine, but the gender issue in DM has been scarcely explored so far. Gender differences have been reported in the incidence and the prevalence of DKD, in its phenotypes and clinical manifestations, as well as in several risk factors, with a different impact in the two genders. Hormonal factors, especially estrogen loss, play a significant role in explaining these differences. Additionally, the impact of sex chromosomes as well as the influence of gene–sex interactions with several susceptibility genes for DKD have been investigated. In spite of the increasing evidence that sex and gender should be included in the evaluation of DKD, several open issues remain uncovered, including the potentially different effects of newly recommended drugs, such as SGLT2i and GLP1Ras. This narrative review explored current evidence on sex/gender differences in DKD, taking into account hormonal, genetic and clinical factors. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

15 pages, 2400 KiB

Open AccessReview

Kidney Biopsy in Type 2 Diabetic Patients: Critical Reflections on Present Indications and Diagnostic Alternatives

by Domenico Santoro, Massimo Torreggiani, Vincenzo Pellicanò, Valeria Cernaro, Roberta Maria Messina, Elisa Longhitano, Rossella Siligato, Guido Gembillo, Ciro Esposito and Giorgina Barbara Piccoli

Int. J. Mol. Sci. 2021, 22(11), 5425; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115425 - 21 May 2021

Cited by 25 | Viewed by 4368

Abstract

Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20–30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed “diabetic kidney disease” without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

20 pages, 935 KiB

Open AccessReview

Kidney Disease in Diabetic Patients: From Pathophysiology to Pharmacological Aspects with a Focus on Therapeutic Inertia

by Guido Gembillo, Ylenia Ingrasciotta, Salvatore Crisafulli, Nicoletta Luxi, Rossella Siligato, Domenico Santoro and Gianluca Trifirò

Int. J. Mol. Sci. 2021, 22(9), 4824; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094824 - 01 May 2021

Cited by 33 | Viewed by 7289

Abstract

Diabetes mellitus represents a growing concern, both for public economy and global health. In fact, it can lead to insidious macrovascular and microvascular complications, impacting negatively on patients’ quality of life. Diabetic patients often present diabetic kidney disease (DKD), a burdensome complication that can be silent for years. The average time of onset of kidney impairment in diabetic patients is about 7–10 years. The clinical impact of DKD is dangerous not only for the risk of progression to end-stage renal disease and therefore to renal replacement therapies, but also because of the associated increase in cardiovascular events. An early recognition of risk factors for DKD progression can be decisive in decreasing morbidity and mortality. DKD presents patient-related, clinician-related, and system-related issues. All these problems are translated into therapeutic inertia, which is defined as the failure to initiate or intensify therapy on time according to evidence-based clinical guidelines. Therapeutic inertia can be resolved by a multidisciplinary pool of healthcare experts. The timing of intensification of treatment, the transition to the best therapy, and dietetic strategies must be provided by a multidisciplinary team, driving the patients to the glycemic target and delaying or overcoming DKD-related complications. A timely nephrological evaluation can also guarantee adequate information to choose the right renal replacement therapy at the right time in case of renal impairment progression. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

10 pages, 999 KiB

Open AccessReview

SGLT2is and Renal Protection: From Biological Mechanisms to Real-World Clinical Benefits

by Giovanna Leoncini, Elisa Russo, Elisabetta Bussalino, Cecilia Barnini, Francesca Viazzi and Roberto Pontremoli

Int. J. Mol. Sci. 2021, 22(9), 4441; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094441 - 23 Apr 2021

Cited by 26 | Viewed by 3458

Abstract

In recent years, following the publication of results from several RCTs, first on cardiovascular and more recently on renal outcomes, SGLT2is have become the standard of care to prevent diabetic kidney disease and slow its progression. This narrative review focuses on biological mechanisms, both renal and extrarenal, underlying kidney protection with SGLT2is. Furthermore, data from cardiovascular as well as renal outcome trials, mostly conducted in diabetic patients, are presented and discussed to provide an overview of current uses as well as the future therapeutic potential of these drugs. Full article

(This article belongs to the Special Issue Novel Aspects in Kidney Disease in Diabetes)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Novel Aspects in Kidney Disease in Diabetes

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Related Special Issue

Published Papers (13 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI